Side effects and placebo amplification.

A sample of placebo-controlled tricyclic antidepressant studies was examined retrospectively to determine whether there was any difference in the relative efficacy of the tricyclic when it was compared against an inert placebo as against an active (atropine) placebo with anticholinergic side effects. Fewer studies showed a significant difference between atropine placebo and drug than between inert placebo and drug. The possibilities that atropine has a specific antidepressant effect, or that side effects amplify placebo responses are considered.